Injectable nanoparticles/hydrogels composite as sustained release system with stromal cell-derived factor-1α for calvarial bone regeneration

Abstract

Repair of craniofacial bony defects remains a challenge for surgeons due to the delicate and complex anatomy of the craniofacial skeleton. Stromal cell-derived factor-1α (SDF-1α) is an important chemokine which plays a critical role in the homing of mesenchymal stem cells (MSC), while, the shortcomings including short half-life and easy degradation by enzymes made it in relatively low efficacy. In this work, SDF-1α/chitosan/carboxymeymethy-chitosan nanoparticles (SDF-1α/CS/CMCS NPs) were prepared and characterized for various parameters including morphology, particle size, zeta potential, loading efficiency and the release characteristics from thermosensitive chitosan/β-glycerol phosphate disodium salt (CS/GP) hydrogels. The SDF-1α encapsulated in CS/CMCS NPs within CS/GP hydrogels showed significantly sustained release effect. The cumulative release of SDF-1α was only 40% during 28d. The data from rat calvarial defects model revealed that the SDF-1α/CS/CMCS NPs embedded hydrogels group could significantly promote the new bone formation (38.5±4.5%), compared to that of the SDF-1α embedded hydrogels group (26.3±7.25%, p<0.05) and the control group (8.64±4.8%, p<0.01). Histological data also confirmed this difference. This study demonstrated the potential applications of nanoparticulate injectable hydrogels for sustained release SDF-1α on bone tissue regeneration.

Keywords: Bone regeneration; Chitosan; Hydrogels; Nanoparticles; Stromal cell-derived factor-1α.